Severe SARS-CoV-2 infection Infections and Infestations
Conditions
Interventions
Study participants will be randomly allocated to receive one of the following at Visit 1: a 4th dose of either Pfizer/Wyeth or AstraZeneca/Fiocruz vaccines, =6 months after heterologous or homologous
Sponsors
University of Oxford
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Participants in study RHH_001 per-protocol population who were fully evaluable. Participants included in previous neutralization assay subsets will be targeted for enrolment first if operationally feasible. 2. Willing and able to provide informed consent prior to any study procedure 3. Willing and able to comply with the study procedure 4. Received heterologous or homologous third vaccine dose =6 months prior to this study 5. For people of childbearing potential: 5.1. Willing to practice continuous effective contraception during the study 5.2. Negative pregnancy test on the day(s) at screening Additional inclusion criteria for part 2 only: 1. Informed consent to receive 4th vaccine dose, AstraZeneca/Fiocruz or Pfizer/Wyeth 2. No contraindication against AstraZeneca/Fiocruz or Pfizer/Wyeth SARS-C0V-2 vaccine
Exclusion criteria
Exclusion criteria: 1. Any additional SARS-CoV-2 vaccine after the 3rd dose in study RHH_001 2. Fever >37.5 °C (axillary) or any acute disease at baseline (Day 0) or within the 3 days prior to randomization. Febrile participants with mild diseases may be enrolled at the investigator’s discretion once fever has resolved. 3. Participants with a history of serious vaccine-related adverse reaction or serious allergic reaction (e.g. anaphylaxis) to any study vaccine component, as described in the last summary of product characteristics for AstraZeneca/Fiocruz or Pfizer/Wyeth 4. Known bleeding disorder that, in the investigator’s opinion, would contraindicate intramuscular injection 5. Any progressive or serious neurological disorder, seizure disorder, or history of Guillian-Barré syndrome 6. Given treatment with immunosuppressant therapy within the last 90 days, including cytotoxic agents or systemic corticosteroids, or planned receipt during the study period. If a short-term cycle of immunosuppressant systemic corticosteroid dose has been used to treat acute disease, the participant should not be enrolled in the study until corticosteroid therapy has been discontinued for =15 days prior to the first study vaccination. In case the participant has been on an immunosuppressant dose of a depot, intramuscular or intra-articular corticosteroid, they should wait 60 days for their enrolment in the study. Inhaled/nebulized, intra-articular, intrabursal or topical (skin or eyes) corticosteroids are allowed. 7. Autoimmune diseases other than: Hashimoto thyroiditis, vitiligo, psoriasis, discoid lupus, and similar diseases. 8. HIV-positive and/or in treatment for HIV 9. Given any other investigational product within the 30 days prior to Day 1, or intending to take part in another clinical trial at any time during this study conduction 10. Given any other licensed vaccine within 14 days prior to enrolment in this study or planning to receive any vaccine up to 28 days after vaccination 11. Given treatment with Rituximab or any other anti-CD20 monoclonal antibody within 9 months prior to Day 1 or planned during the study period 12. Administration of intravenous immunoglobulins and/or any blood products within 3 months prior to enrolment or planned dosing during the study period 13. Participants with any condition that, in the investigator’s opinion, could interfere with the status primary objectives or represent an additional risk for the participant Temporary exclusion criteria: 1. Participants with a recent history of COVID-19 (=4 weeks prior to visit 1) will be delayed until 4 weeks after diagnosis
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part 1: 1. Anti-Spike IgG antibody titers of SARS-CoV-2 measured using blood samples collected at =6 months after the 3rd vaccine dose Part 2: 1. Anti-Spike IgG antibody titers of SARS-CoV-2 measured using blood samples collected at ~28 days after the 4th vaccine dose 2. Neutralizing titer (NT) against SARS-CoV-2 (including against relevant variants of concern) measured using blood samples collected at 28 days and 6 months after the 4th vaccine dose (in a sub-set of participants) | — |
Secondary
| Measure | Time frame |
|---|---|
| Part 1: 1. Neutralizing titer (NT) against SARS-CoV-2 Wuhan strain measured using blood samples collected at =6 months after the 3rd vaccine dose 2. Neutralizing titer (NT) against SARS-CoV-2 (including but not limited to delta and omicron variants) measured using blood samples collected at =6 months after the 3rd vaccine dose Part 2: 1. Anti-Spike IgG antibody titers of SARS-CoV-2 measured using blood samples collected at 28 days and 6 months after the 4th vaccine dose 2. Neutralizing titer (NT) against SARS-CoV-2 (including relevant variants of concern) measured using blood samples collected at 28 days and 6 months after the 4th vaccine dose (in a sub-set of participants) 3. Safety measured using the occurrence of local and systemic Adverse Events (AEs) reported within 7 days after study vaccination (per subgroup) 4. Safety measured using the occurrence of unsolicited severe Adverse Events (AEs) reported within 28 days after study vaccination (per subgroup) 5. Safety measured using the occurrence of Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) recorded within 28 days and up to 6 months after study vaccination (per subgroup). | — |
Countries
Brazil
Outcome results
None listed